Healthy Siblings Research Articles

Children with autism show differences in the gut DNA virome compared to non-autistic children: a case control study

BackgroundSeveral previous studies have identified a potential role that the gut microbiome can play in autism spectrum disorder (ASD) in children, but little is known about how variations in the virome may be involved in ASD. We aimed to understand the changes in the gut DNA virome of children with ASD.MethodsA case–control study was presented, in which 13 two-children families were observed while considering the age, mode of birth, history of antibiotic use, and vaccination history to minimize the influence of confounding factors. DNA viral metagenomic sequencing was successfully performed on stool samples from 11 children with ASD and 12 healthy non-ASD children. The basic composition and gene function of the participants' fecal DNA virome were detected and analyzed. Finally, the abundance and diversity of the DNA virome of children with ASD and their healthy siblings were compared.ResultsThe gut DNA virome in children aged 3–11 years was found to be dominated by the Siphoviridae family of Caudovirales. The proteins encoded by the DNA genes mainly carry out the functions of genetic information transmission and metabolism. Compared the gut DNA virome of ASD and healthy non-ASD children, their abundance of Caudovirales and Petitvirales both showed a significant negative correlation (r = -0.902, P < 0.01), there was no statistically significant difference in the relative abundance of viruses at the order and family levels, and a difference in the relative abundance at the genus level for Skunavirus (Ζ = -2.157, P = 0.031). Viral α diversity was reduced in children with ASD, but α diversity and β diversity did not differ statistically between groups.ConclusionsThis study indicates that elevated Skunavirus abundance and decreased α diversity in the gut DNA virulence group of children with ASD, but no statistically significant difference in the change in alpha and beta diversity. This provides preliminary cumulative information on virological aspects of the relationship between the microbiome and ASD, and should benefit future multi-omics and large sample studies on the gut microbes in children with ASD.

Generation of three induced pluripotent stem cell lines from a patient with KCNQ2 developmental and epileptic encephalopathy as a result of the pathogenic variant c.638C > T; p.Arg213Gln (NUIGi063-A, NUIGi063-B, NUIGi063-C) and 3 healthy controls (NUIGi064-A, NUIGi064-B, NUIGi064-C)

KCNQ2 encodes the potassium-gated voltage channel Kv7.2, responsible for the M−current, which contributes to neuronal resting membrane potential. Pathogenic variants in KCNQ2 cause early onset epilepsies, developmental and epileptic encephalopathies. In this study, we generated three iPSC lines from dermal fibroblasts of a 5 year-old female patient with the KCNQ2 c.638C > T (p.Arg213Gln) pathogenic heterozygous variant and three iPSC lines from a healthy sibling control. These iPSC lines were validated by confirming the targeted mutation, SNP karyotyping, STR analysis, pluripotent gene expression, differentiation capacity into three germ layers, and were free of transgene integration and Mycoplasma.

Providing information about a child's oncological disease - a challenge for a pediatric oncologist

Introduction: The diagnosis of a serious illness in a family affects all members. The child is a special subject, as he cannot yet understand many aspects of life at such a high perceptual level as an adult. Communicating difficult information is part of the doctor's task and is one of the most difficult parts of the therapeutic process. &#x0D; The aim of the study: To analyze the methodology of communicating difficult information to pediatric oncology patients.&#x0D; Material and method: Polish and English-language scientific literature from 2012 - 2022 from databases such as PubMed, SCOPUS, Google Scholar, Web of Science was reviewed. Searches were conducted according to keywords: communicating difficult information, oncology, pediatrics, physician.&#x0D; Results and conclusions: One of the most well-known protocols for communicating difficult information is SPIKES. It describes the basic and necessary steps for properly informing parents and the child about the diagnosis, for example. Healthy siblings should also learn about their brother's illness, but this task falls to the parents. Psycho-oncological support for both the child and parents should be holistic, based on best practices, and tailored to the family's needs.&#x0D;

Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: evidence from toddlers

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impaired social and communication skills, narrow interests, and repetitive behavior. It is known that the cerebellum plays a vital role in controlling movement and gait posture. However, recently, researchers have reported that the cerebellum may also be responsible for other functions, such as social cognition, reward, anxiety, language, and executive functions.MethodsIn this study, we ascertained volumetric differences from cerebellar lobular analysis from children with ASD, ASD siblings, and typically developing healthy controls. In this cross-sectional study, a total of 30 children were recruited, including children with ASD (N = 15; mean age = 27.67 ± 5.1 months), ASD siblings (N = 6; mean age = 17.5 ± 3.79 months), and typically developing children (N = 9; mean age = 17.67 ± 3.21 months). All the MRI data was acquired under natural sleep without using any sedative medication. We performed a correlation analysis with volumetric data and developmental and behavioral measures obtained from these children. Two-way ANOVA and Pearson correlation was performed for statistical data analysis.ResultsWe observed intriguing findings from this study, including significantly increased gray matter lobular volumes in multiple cerebellar regions including; vermis, left and right lobule I–V, right CrusII, and right VIIb and VIIIb, respectively, in children with ASD, compared to typically developing healthy controls and ASD siblings. Multiple cerebellar lobular volumes were also significantly correlated with social quotient, cognition, language, and motor scores with children with ASD, ASD siblings, and healthy controls, respectively.ConclusionsThis research finding helps us understand the neurobiology of ASD and ASD-siblings, and critically advances current knowledge about the cerebellar role in ASD. However, results need to be replicated for a larger cohort from longitudinal research study in future.

5595849 THE GUT MICROBIOME AND HYDROXYUREA EFFECT ON SICKLE CELL DISEASE CHILDREN FROM ANGOLA

Background: Sickle cell disease (SCD) is an inherited hematological disorder and a serious global health problem, affecting between 20 and 25 million people worldwide [1]. In the Sub-Saharan Africa, where it is more prevalent, it contributes up to 90% of under-5 mortality [2]. Although hydroxyurea (HU) is the leading treatment for these patients, its effects on the gut microbiome have not yet been explored. Some studies reported that gastroenteritis events were less frequent in SCA children taking HU and it also significantly improved the survival from pneumococcal infections [3,4]. HU may have a protective effect, not only by improving several hematological parameters but also by lowering the risk of some bacterial infections. Aims: In this context, the aim of this study was to investigate this association by characterizing the gut microbiome of an Angolan SCA pediatric population before and after 6 months of HU treatment and comparing with a control group of healthy siblings. Results: A total of 113 fecal samples were obtained and sequenced by NGS for the 16S rRNA gene (V3-V4 regions), which corresponded to 40 children in the control and before HU groups and 33 after HU, aged between 4-12 years old. Our findings revealed that these three groups exhibit some notable differences, especially within Lachnospiraceae and Ruminococcaceae family. After HU treatment there was an increase of several beneficial bacteria, such as: Blautia coccoides (p=0.009), Blautia luti (p<0.001), Blautia faecis (p=0.008), Bifidobacterium longum (p=0.011), Dorea formicigenerans (p<0.001), Dorea massiliensis (p=0.003), Eubacterium halii (p=0.004), Elusimicrobium spp (p=0.032), Ruminococcus callidus (p=0.037), Ruminococcus faecis (p=0.012), Roseburia spp (p=0.050) and Subdoligranulum variabile (p=0.009). Most of those OTUs are SCFAs producing species, having butyrate or propionate as end-products of bacterial metabolism, both exhibiting anti-inflammatory properties. Moreover, children before HU had higher abundance of bacteria considered pathogenic, like E. coli (p=0.001), Clostridiun_g24 (p=0.039) and H. influenzae (p=0.050). Conclusion: Overall, this study provides the first evidence of the HU effect on the gut microbiome and provides a rationale for further research for developing treatments to reduce gut microbiota-driven inflammation, which may attenuate the dysbiosis and chronic symptoms experienced by these patients. This work was supported by FCT/Aga Khan (project nº330842553) and FCT/MCTES (UIDB/05608/2020 and UIDP/05608/2020) –H&TRC.

Investigation of the Relationship Between Cognitive Functions and Retinal Findings From Spectral Optical Coherence Tomography in Patients With Schizophrenia and Their Healthy Siblings.

Retinal structural changes which were investigated by optical coherence tomography (OCT) have been reported in schizophrenia. Since cognitive dysfunction is a core feature of schizophrenia, the correlations between retinal findings and cognitive functions of patients and their healthy siblings may provide insight into the pathophysiological processes of the disorder. We aimed to investigate the relationship between neuropsychiatric tests and retinal changes in schizophrenia patients and their healthy siblings. We measured OCT parameters and cognitive performance (via Trail Making Tests, verbal fluency tests, and The Digit Span Tests) of 72 participants (36 patients with schizophrenia and 36 healthy siblings) and disease severity (with Positive and Negative Syndrome Scale, Global Assessment of Functioning, and Clinical Global Impression scales) in patients with schizophrenia and evaluated the relationship between retinal findings and clinical parameters, especially neurocognitive tests. We found decreased ganglion cell layer-inner plexiform layer thickness and macular volume in the patient group. There were strong correlations between neurocognitive tests and OCT findings in both groups. On the other hand, there was not any correlation between retinal findings and disease parameters. The cognitive symptoms of schizophrenia may be more closely related to structural changes in the retina.

Integrated glycomics and genetics analyses reveal a potential role for N-glycosylation of plasma proteins and IgGs, as well as the complement system, in the development of type 1 diabetes

Aims/hypothesisWe previously demonstrated that N-glycosylation of plasma proteins and IgGs is different in children with recent-onset type 1 diabetes compared with their healthy siblings. To search for genetic variants contributing to these changes, we undertook a genetic association study of the plasma protein and IgG N-glycome in type 1 diabetes.MethodsA total of 1105 recent-onset type 1 diabetes patients from the Danish Registry of Childhood and Adolescent Diabetes were genotyped at 183,546 genetic markers, testing these for genetic association with variable levels of 24 IgG and 39 plasma protein N-glycan traits. In the follow-up study, significant associations were validated in 455 samples.ResultsThis study confirmed previously known plasma protein and/or IgG N-glycosylation loci (candidate genes MGAT3, MGAT5 and ST6GAL1, encoding beta-1,4-mannosyl-glycoprotein 4-beta-N-acetylglucosaminyltransferase, alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase and ST6 beta-galactoside alpha-2,6-sialyltransferase 1 gene, respectively) and identified novel associations that were not previously reported for the general European population. First, novel genetic associations of IgG-bound glycans were found with SNPs on chromosome 22 residing in two genomic intervals close to candidate gene MGAT3; these include core fucosylated digalactosylated disialylated IgG N-glycan with bisecting N-acetylglucosamine (GlcNAc) (pdiscovery=7.65 × 10−12, preplication=8.33 × 10−6 for the top associated SNP rs5757680) and core fucosylated digalactosylated glycan with bisecting GlcNAc (pdiscovery=2.88 × 10−10, preplication=3.03 × 10−3 for the top associated SNP rs137702). The most significant genetic associations of IgG-bound glycans were those with MGAT3. Second, two SNPs in high linkage disequilibrium (missense rs1047286 and synonymous rs2230203) located on chromosome 19 within the protein coding region of the complement C3 gene (C3) showed association with the oligomannose plasma protein N-glycan (pdiscovery=2.43 × 10−11, preplication=8.66 × 10−4 for the top associated SNP rs1047286).Conclusions/interpretationThis study identified novel genetic associations driving the distinct N-glycosylation of plasma proteins and IgGs identified previously at type 1 diabetes onset. Our results highlight the importance of further exploring the potential role of N-glycosylation and its influence on complement activation and type 1 diabetes susceptibility.Graphical abstract

A262 NEONATAL ACUTE LIVER FAILURE DUE TO PRESUMED GESTATIONAL ALLOIMMUNE LIVER DISEASE - A CASE REPORT

Abstract Background Neonatal acute liver failure (NALF) is a rare disease that is distinct from acute liver failure seen in older children and adults. Gestational alloimmune liver disease (GALD) is the most frequent cause, is initiated in utero by sensitization of the maternal immune system to a fetal hepatocyte antigen and subsequent production of maternal immunoglobulin G antibodies that cross the placenta. Maternal IgG binds to a fetal hepatocyte antigen and initiates an innate immune response involving the terminal complement cascade and membrane attach complex. The understanding of the alloimmune origin has led to the use of intravenous immunoglobulin (IVIG) treatment and exchange transfusion, significantly increasing survival. However, approximately 25% of patients may not respond and require salvage liver transplantation. In spite of an increased rate of comorbidities, concern for technical difficulties and limited graft availability, young infants eligible for transplant have been shown to have similar overall patient and graft survival rates compared to older children with other indications for liver transplant. Purpose The primary aim of our study is to report a case of NALF with successful liver transplant. Method We present the case of a preterm girl with NALF due to GALD refractory to medical management, requiring liver transplantation. Result(s) This is a 35-week preterm girl, with scant pre-natal care, birth weight of 1.825 kg and Apgar 9/9. She is the seventh child of non-consanguineous parents, with healthy siblings. On day-of-life (DOL) 1 she presented with acute kidney injury, progressive worsening metabolic acidosis and hyperammonemia and was found to be profoundly coagulopathic (INR 6), with normal liver enzymes and liver failure was diagnosed. Initial investigation ruled out congenital infections, sepsis, neonatal hemophagocytic lymphohistiocytosis and metabolic diseases. Magnetic resonance imaging of the body demonstrated findings in keeping with iron deposition in the thyroid, liver and pancreas, suggestive of GALD. Completed double volume exchange transfusion and IVIG on DOL 9 and repeat IVIG on DOL 13 and 15, with partial improvement in INR. Due to persistent ascites, conjugated hyperbilirubinemia and hyperammonemia she was transferred for urgent liver transplant assessment. Persistent liver dysfunction in the form of hyperammonemia, hypoglycemia and progressive coagulopathy led to transplant listing on DOL 30. ABO incompatible deceased donor liver transplant was completed on DOL 62 (4.075 kg, estimated dry weight 3.5 kg). The procedure was uncomplicated, liver enzymes normalized, coagulopathy and hypoglycemia resolved. She was transferred to the ward on post-operative day (POD) 6. and weaned off sedatives and transitioned to oral feeds within 2 weeks of transplant, with complex abdominal wound closure on POD 29. Conclusion(s) Successful liver transplantation is possible in neonates with acute liver failure due to GALD refractory to medical management and weighing 4kg or less. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared MICROBIOME &amp; MICROBIAL THERAPY

Sleep disorders in patients with a first psychotic episode: a case-control study

Introduction Patients with chronic schizophrenia experience significant disturbances in the quality and quantity of their sleep and it had been mainly attributed to severity of symptoms and antipsychotic use. Recent studies suggested that antipsychotic-naïve early course patients with schizophrenia and their non-psychotic first-degree relatives also show altered sleep quality. Objectives In this study we aimed to compare sleep parameters in antipsychotic-naive first-episode schizophrenia patients to their healthy siblings and age- and sex-matched healthy controls. Methods We conducted a cross-sectional, descriptive case-control study in the Psychiatry « G » department at Razi Hospital, for a period of six months. Our sample consisted of three groups: a group of schizophrenic patients, a group of their healthy siblings and a group of healthy controls. The three groups were matched by age and sex. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of symptoms in patients with schizophrenia. The Morningness-Eveningness Questionnaire (MEQr), Epworth Sleepiness Scale (ESS), and Pittsburgh Sleep Quality Index (PSQI) were used in the three groups to assess Circadian preference, daytime sleepiness and sleep quality. Results There was no significant difference between the groups regarding the chronotype. Patients had significantly higher daytime sleepiness compared to siblings (p=0.001) and controls (p&lt;0.001). Patients also had poorer quality sleep (PSQI total score) than siblings (p&lt;0.001) and controls (p&lt;0.001), longer sleep latency than siblings (p=0.003) and controls (p&lt;0.001); lower habitual sleep efficiency than siblings (p=0.003) and controls (p&lt;0.001). Siblings had poorer sleep quality (p=0.001), longer sleep latency (p=0.006) and shorter sleep duration (p=0.033) compared to control subjects. Conclusions Our results joined those of the literature concerning the significant prevalence of sleep disorders in early psychosis. In addition, the alteration of sleep quality in unaffected siblings compared to healthy controls supports the hypotheses suggested in the literature that sleep disorders may be markers of genetic susceptibility to schizophrenia and serve as a potential endophenotype of the disease. Disclosure of Interest None Declared

Subclinical memory impairment in unaffected siblings of patients with dementia

Objective: Family history of dementia is a known risk factor for dementia. The cognitive performance of unaffected siblings of dementia patients has been poorly studied. We aimed to determine whether clinically unaffected siblings of dementia patients have significant cognitive impairment compared to individuals who do not have first-degree relatives with dementia. Methods: We compared the cognitive performance of 67 patients with dementia (24 males; mean age 69.5), 90 healthy siblings of those patients (34 males; mean age 61.56) and 92 healthy adults (35 males; mean age 60.96) who have no first-degree relatives with dementia. We assessed learning and memory (Rey Auditory Verbal Learning Test (RAVLT)), short-term/working memory (Digit Span) executive functions (Stroop Test) and general intelligence (Raven Progressive Matrices). Test scores were compared among three groups, with regression-based adjustments for age, sex, and education. Results: As expected, the patients with dementia were impaired in all cognitive domains. In the Sibling Group, RAVLT total learning was significantly lower compared to controls (B = −3.192, p = .005). In a subgroup analysis, compared to controls, RAVLT delayed recall was poorer in the siblings of patients with early-onset (<65 years) dementia. No significant differences were observed in other cognitive domains. Conclusion: Clinically unaffected siblings of dementia patients seem to have a selective subclinical impairment in memory encoding. This impairment seems to be more prominent in siblings of patients with early-onset dementia who also have deficits in delayed recall. Future studies are needed to determine if the observed cognitive impairment deteriorates to dementia.

Technology-Mediated Support Among Siblings of Children with Cancer.

Purpose: A diagnosis of pediatric cancer can leave healthy siblings with limited access to support. Technology-mediated interpersonal interactions have been noted among adolescent and young adults with cancer and may be an effective source of support for adolescent siblings of children with cancer. In this study, we understand how adolescent siblings use technology to connect with their support network and how their technology use changes after their sibling's cancer diagnosis. Methods: Participants included a national sample (N = 24) of adolescents aged 12-17 who had a sibling diagnosed with cancer in the last 2 years (up to 3 years if still receiving curative-focused treatment). Ecomaps were cocreated with participants to identify sources of social support and modality of interactions. Interviews were transcribed, coded, content analyzed, and descriptively summarized. Results: Adolescent siblings (mean = 14.2 years) perceived technology as a tool to maintain support from their established personal network, rather than a way to expand sources of social support. Most did not seek support or information about cancer outside their known network, preferring information to come from parents or trusted network members. Siblings identified video calls as an important resource for connecting with parents, their sick brother or sister, and others to receive emotional support and companionship. Conclusions: Findings suggest that adolescent siblings of children use technology to connect with their established network for support, an important finding for designing assessments and interventions for this population. Future inquiry should explore these differences, identify unmet needs, and inform acceptable, effective interventions to augment support.

Do We Need Palliative Care in Pediatric Nephrology? Patients' and Caregivers' Disease Experience.

Chronic life-limiting illnesses such as chronic kidney disease (CKD) require integral support to the families concerned in addition to medical care. Palliative care is an option to facilitate families to address future concerns, such as procedures for acute life-threatening complications, or to relieve physical and psychosocial suffering. The exact needs of patients or parents have not yet been investigated. To assess needs in supportive palliative care, we conducted a monocentric qualitative interview study. We included patients 14 to 24 years old as well as parents of younger children (below 14 years) with CKD ≥ stage 3. In total, fifteen interviews were conducted. Data were analyzed with a deductive and descriptive approach using qualitative content analysis as described by Mayring. Sociodemographic data and basic information of disease were collected using questionnaires. In contrast to caregivers, adolescents and young adults do not express worries about their own mortality or reduced life expectancy. Rather, they report about their limitations to everyday life associated with the disease, especially in the areas of school and work. They wish to live a normal life. Caregivers are concerned about the future and the disease trajectory. They also describe difficulties in balancing the management of the disease with other responsibilities such as work and healthy siblings' needs. Patients and caregivers appear to need a chance to talk about their everyday struggles and disease-related fears and concerns. Talking about their concerns and needs may help deal with their emotions and facilitate acceptance of their situation characterized by a life-limiting disease. Our study confirms the need for psychosocial support in pediatric nephrology to address the needs of the affected families. This can be offered by pediatric palliative care teams.

Increased levels of anti-BSA antibodies in children with Down syndrome.

Autoimmune diabetes occurs more often in the first 2 years of life in children with Down syndrome (DS) compared with the general population. We previously observed increased frequencies of islet autoantibodies, including insulin autoantibodies (IAA), in children with DS. Assays for IAA using 125I-labelled insulin require competition to overcome cross reactivity with antibodies to the cow's milk protein, bovine serum albumin (BSA). 125I-IAA assay results suggested that levels of antibodies to BSA may also be increased in children with DS. The aim of this study therefore was to determine whether the levels of anti-BSA antibodies differed in children with DS compared with controls. Samples were available from two populations with DS: one from the UK, (UK DS cohort n=106, 58 male, median age 12.5 years) and one from Estonia (Estonian DS cohort: n=121, 65 male, median age 9.75 years). A UK control population was provided by sex and age-matched healthy siblings of probands participating in the Bart's Oxford (BOX) family study of type 1 diabetes. A competitive-displacement radiobinding assay (RBA) and a Dissociation Enhanced Lanthanide Fluoroimmunoassay (DELFIA) were developed to measure and confirm anti-BSA antibody levels. HLA class II genotype was analysed by PCR using sequence specific primers (PCR-SSP). Overall, levels of anti-BSA antibodies were increased in those with DS compared with controls (p<0.0001) but this was not HLA associated. Increased levels of anti-BSA antibodies may reflect a defect in immune maturation or increased gut permeability in children with DS, increasing their risk of developing autoimmunity.

Interviews with children and adolescents with epilepsy or asthma about the situation of their healthy siblings.

Chronic conditions can influence the situation of healthy siblings of affected children. We investigated the opinion of the affected child about the situation of their healthy sibling and the sibling relationship. We performed a semi-structured interview with epilepsy or asthma patients aged 6-18 years and asked them to draw a picture: "Epilepsy/Asthma, my siblings and me." Of the 58 children with epilepsy, 67%, and of the 40 children with asthma, 60% thought that their siblings were worried about the condition. Among other aspects, they addressed helplessness during a seizure. Of the children with epilepsy, 83% and of those with asthma, 95% assumed that their siblings were not disadvantaged because of the participant's condition. Of the patients with epilepsy, 91% and of those with asthma, 93% thought that the sibling relationship would not be different without the condition. Of the participants with epilepsy, 86% and of those with asthma, 93% drew a picture; 30% with epilepsy and 14% with asthma visualised an interaction with their siblings in context of a seizure or episode of dyspnoea. According to the affected children, the condition worries their siblings but does not affect the siblings' lives or the sibling relationship.

An insulin hypersecretion phenotype precedes pancreatic β cell failure in MODY3 patient-specific cells.

MODY3 is a monogenic hereditary form of diabetes caused by mutations in the transcription factor HNF1A. The patients progressively develop hyperglycemia due to perturbed insulin secretion, but the pathogenesis is unknown. Using patient-specific hiPSCs, we recapitulate the insulin secretion sensitivity to the membrane depolarizing agent sulfonylurea commonly observed in MODY3 patients. Unexpectedly, MODY3 patient-specific HNF1A+/R272C β cells hypersecrete insulin both invitro and invivo after transplantation into mice. Consistently, we identified a trend of increased birth weight in human HNF1A mutation carriers compared with healthy siblings. Reduced expression of potassium channels, specifically the KATP channel, in MODY3 β cells, increased calcium signaling, and rescue of the insulin hypersecretion phenotype by pharmacological targeting ATP-sensitive potassium channels or low-voltage-activated calcium channels suggest that more efficient membrane depolarization underlies the hypersecretion of insulin in MODY3 β cells. Our findings identify a pathogenic mechanism leading to β cell failure in MODY3.

Behavioral problems in infants and young children with spinal muscular atrophy and their siblings: A cross-sectional study.

Older children and adults with spinal muscular atrophy (SMA) have been shown to have more anxiety, depression, and other behavioral problems in a few studies. But no similar studies have been performed in infants and young children with SMA. Behavioral co-morbidities of young children with SMA were compared with healthy and children with chronic non-neurological illness control group. Infant Behavior Questionnaire-Revised (IBQ-R) and parent-report version of chid behavior checklist (CBCL) were used for infants and preschool-age children respectively. A total of 35 SMA children (age at symptom onset-5.9±2.8 months, at enrolment-21.4±7.1 months, 65% boys, 11, 19 and 5 were SMA 1, 2 and 3 respectively) and 24 siblings (38.6±11.2 months, 71% boys) were enrolled. We also enrolled 15 children with nephrotic syndrome as age and gender matched control to SMA children in age-group 2-5 years (27.7±9.1 months, 67% boys). In infants with SMA, the scale scores of IBQ-R were significantly higher for distress to limitation, fear, sadness, and falling reactivity/rate of recovery from distress (p=0.005; 0.03; 0.001, and 0.04) and lower for soothability as compared to healthy control group (p=0.04). Similarly, for the three dimensions of temperament computed from these 13 domains, the mean scale score for surgency/extraversion was lower and negative affectivity was higher (p=0.04 and 0.03), in infants with SMA as compared to healthy controls. For preschool age group, the internalizing problem scores (p=0.009 and 0.03) and stress problem scores (p=0.002 and 0.04) were higher in the SMA group, as compared to both the healthy control group and diseased control group. While assessing the syndrome scale scores, the score was higher for emotionally reactive (p=0.0002 and 0.01) and anxious domains (p<0.0001 and p=0.0002) compared to both healthy and diseased control groups. Infants and young children with SMA suffer from increased internalizing problems like anxiety, depression and probably their healthy siblings are also at increased levels of stress, depicted by increased somatic complaints.

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings.

One of the most common children's endocrine and autoimmune diseases in the world is type 1 diabetes mellitus (T1DM). The incidence of type 1 diabetes is constantly increasing, and according to current estimates, the number of children with T1DM in the world has exceeded 542,000. There are 3 main components emphasized in the pathogenesis: genetic and environmental factors, and the patient's immune system. Many publications have confirmed the role of natural killer cells (NK) in the pathogenesis of type 1 diabetes and other autoimmune diseases. The aim of the study was to evaluate the population of NK cells and pancreatic β cell autoantibodies in a group of children with T1DM and their healthy siblings in comparison with children from families with no history of autoimmune diseases. The research included 76 children with T1DM, 101 children from the sibling group, and 30 children from the control group. Peripheral blood was analysed on a FACSCalibur flow cytometer (Becton Dickinson) to evaluate the NK cell population. The results were presented as the percentage of NK cells among lymphocytes. Statistical analysis was performed using STATIS-TICA 10 PL software. The mean percentage of NK cells in children with T1D (10.59 ±5.37) and in the sibling group (11.93 ±5.62) was statistically reduced in comparison to the control group (14.89 ±7.78) in sequence (Student's t -test: t = -3.24; df = 103; p = 0.002) (Stu-dent's t -test: t = -2.30; df = 128; p = 0.02). There was no statistically significant difference in the percentage of NK cells be-tween the group of children with T1DM and their siblings (Student's t -test: t = -1.59; df = 173; p = 0.11). In the group of sib-lings, the younger the child, the lower the reported percentage of NK cells. This relationship was statistically significant (test for the Pearson correlation coefficient t = 3.41; p = 0.0009; r = 0.33). In the group of children with type 1 diabetes, a similar relationship was not found. The concentration of anti-IA2 and anti-Znt8 antibodies was statistically significantly higher in the sibling group compared to the control group (anti-IA2 p = 0.0000001; anti-ZnT8 p = 0.00001), and the concentration of anti-GAD antibodies was comparable in both groups. In the group of children with type 1 diabetes, a positive correlation was demonstrated between the reduced percentage of NK cells and the coexistence of anti-GAD and anti-ZnT8 antibodies (Mann-Whitney U test Z = -2.02; p = 0.04). There was no similar relationship in the group of siblings. The reduced percentage of NK cells in children with T1DM and in their siblings compared to the control group suggests the role of NK cells in the pathogenesis of T1DM. Genetic predisposition and dysfunction of NK cells probably underlie the pathogenesis of T1DM.

The relationship between executive functions and chronotype in healthy siblings of children with autism spectrum disorder

ABSTRACT The aim of this study is to examine executive functions in healthy siblings of children with autism spectrum disorder (ASD) and to evaluate the relationship between chronotype and executive functions (EF). This study included 40 healthy siblings (case group) of children with ASD and 40 healthy controls. Executive functions were evaluated by Stroop Test, Serial Digit Learning Test (SDLT) and Cancellation Test (CT). Children’s Chronotype Questionnaire (CCTQ) and Autism Spectrum Screening Questionnaire (ASSQ) were administered to parents. It was determined that the Stroop Test and CT performances of the case group were significantly worse than the control group. There was no difference in SDLT. It was determined that the total CCTQ score of the case group was significantly higher. In addition, a significant positive correlation was found between the chronotype total score and the number of false targets in the second part of CT. In the logistic regression analysis; the chronotype total score, Stroop test fifth part correction number and CT fourth part error number were determined as possible factors in the differentiation of the case and control groups. More studies are needed to evaluate the relationship between executive functions and chronotype in siblings of children with ASD.

Preventable Prenatal and Neonatal Risk Factors of Type 1 Diabetes in Childhood.

Childhood type 1 diabetes mellitus (T1DM) is an autoimmune disease which is increasing in incidence, but little is known about the events that trigger the autoimmune process. Most of the time, these processes begin in prenatal and natal periods; therefore, this study aimed to investigate the prenatal and neonatal risk factors of T1DM in childhood. This case-control study has been performed on children with T1DM who referred to the 17th Shahrivar children's hospital. The control group consisted of healthy siblings of the case group. Data were gathered using a form that included maternal and neonatal characteristics. Data were reported by descriptive statistics in SPSS 19. To investigate the effect of quantitative and qualitative variables on the development of T1DM, logistic regression and Chi-square tests were used, respectively. Birth weight, birth height, and maternal weight gain during pregnancy had a significant relationship with T1DM (odds ratio [OR] = 1.23, 2.57, and 1.14, respectively). In addition, there was a significant relationship between gestational hypertension (OR = 5.27), neonatal jaundice (OR = 3.42), cesarean section (OR = 2.06), and being non-first-born child (OR = 2.32) and T1DM. Also, premature rupture of membrane, maternal urinary tract infection, and nonexclusive breastfeeding had a significant association with T1DM (OR = 4.37, 3.94, and 2.30, respectively). There were no statistically significant differences between maternal age, sex, neonatal respiratory disease, prematurity, and neonatal infections and T1DM (P > 0.05). Prenatal and neonatal risk factors can have a significant role in the occurrence of TIDM. Therefore, considering these risk factors can have a preventive effect on T1DM.

A Multicenter Network Analysis Examining the Psychological Effects of the COVID-19 Pandemic on Patients with Eating Disorders versus Their Healthy Siblings.

(1) Background: The impact of the COVID-19 pandemic on individuals with eating disorders (EDs) has been recorded all over the world; the traumatic effects of COVID-19 have exacerbated specific and general psychopathologies in those with EDs. Comparing patients' and their healthy siblings' responses might help one evaluate whether there are significant differences between healthy individuals and those struggling with EDs in regard to posttraumatic psychological symptoms. (2) Methods: A sample of 141 ED patients and 99 healthy siblings were enrolled in this study in two different centers specializing in ED treatment. All participants completed the posttraumatic stress disorder (PTSD) checklist and an eating and general psychopathological self-report questionnaire. Network analysis was then applied to evaluate the differences between the populations. (3) Results: No significant differences emerged between the network structures despite the significant differences between patients and their healthy siblings in regard to posttraumatic symptoms, eating, and general psychopathology. (4) Conclusion: The complex nature of the interaction between environmental and personal factors should be evaluated further in individuals with EDs due to how they respond to traumatic events, which exacerbate patients' psychopathology.